Aging with HIV infection

1. Aging with HIV infection Bill Powderly MD School of Medicine and Medical Sciences University College Dublin Ireland

2. Overview • As patients get older, common diseases become more prevalent.  • Relevant impact of varying risk factors is difficult to determine and varies among co-morbidities. • Relationship with HIV or antiretroviral therapy is also variable and of different importance. • Specific examples: cardiovascular disease, bone disease • Implications for management • Implications for future research.

3. Ageing of HIV population Swiss Cohort Hasse et al, CROI 2011, O-161

4. Incidence of Multiple Comorbidities Increases With Age in HIV-Infected Pts No comorbidity 100 Patients (%) 1 comorbidity 2 comorbidities 75 3 comorbidities 4 comorbidities 5 comorbidities 50 25 0 ≤ 30 31-40 41-50 51-60 > 60 Age (Years) Guaraldi G, et al. Glasgow 2008. Abstract P300.

5. Risk of “co-morbidities” increases as individuals get older HIV does not cause these illnesses However HIV and/or ART may increase the risk Interplay of time with morbidity HIV infection Ageing Antiviral treatment

6. HIV Associated Non AIDS Conditions • Usual risk factors determine most of the risk • Increasing age and substance use add to risk • Additonal risk may be due to HIV, to ART or both • May/may not be associated with CD4 or HIV-1 RNA • role of Chronic viral infection • role of Chronic inflammation • Major Issue for HIV researchers: • how important is the additional risk • Are the effects of HIV reversible or preventable • Major issue for HIV providers and patients • Is management different

7. Deeks, Annu. Rev. Med. 2011. 62:141–55

8. Life expectancy at birth (men) World Health Report 2006, Hanlon et al 2006, AIHW 2008

9. FRAM HIV Infection is an independent risk factor for atherosclerosis *p<0.01, **p<0.001, ***p<0.0001; †There was a significant gender interaction Grünfeld C et al. AIDS 2009

10. HIV and Heart disease • Multiple studies show increased risk of MI and other ischemic CV events in HIV infected patients • Risk related to chronic inflammation • Risk related to ART – espec specific PIs and NRTIs • However, most clinical events are seen in patients with other ‘standard’ risk factors • Emphasizes need for routine primary and secondary prevention

11. BMD Changes in normal population Relative influence on peak bone mass (men):40% to 83% genetic 27% to 60% environmental 0.5%-1.0% reduction in bone volume/year Peak 1.0 0.9 0.8 0.7 0.6 Change in Bone Volume (%) 0.5 Men 0.4 0.3 Women 0.2 0.1 0 10 20 40 50 80 0 30 60 70 Age (Years) Orwoll ES, et al. Endocr Rev. 1995;16:87-116.

12. Bone mineral loss and HIV • Multiple cohort studies show increased prevalence of bone demineralization (osteopenia and osteoporosis) in HIV+ patients as compared to controls • Seen in untreated and treated patients • HIV effect - virus or disease • Treatment effect – particularly with initiation

13. Risk Factors for Decreased BMD in HIV-infected Individuals Classic Secondary Decreased physical activity Femalesex Chronic diseases (e.g. hyperthyroidism, hyperparathyroidism, liver disease, rheumatological conditions, eating disorders, etc.) Smoking Decreased bone acquisition White race Hypogonadism Family history Amenorrhoea /premature menopause Renal dysfunction Increasing age Malnutrition/low BMI Alcohol Medications (e.g. corticosteroids, anticonvulsants, anticoagulants) Bone Mineral Density HIV / HAART-related Nucleoside analogues /mitochondrial dysfunction Protease inhibitors Cytokines (eg TNFa, IL6) Diagram adapted from Glesby MJ. Clin Infect Dis 2003; 37(Suppl 2):S91–S95

14. Potential effects of HIV Decreased total bone mass Increased rate of bone demineralization Peak 1.0 0.9 0.8 0.7 0.6 Change in Bone Volume (%) 0.5 Men 0.4 0.3 Women 0.2 0.1 0 10 20 40 50 80 0 30 60 70 Age (Years) Orwoll ES, et al. Endocr Rev. 1995;16:87-116.

15. Fracture Prevalence in HIV-infected and non-HIV-infected Persons MGH/Partners Healthcare System: 1996-2008 Triant, JCEM, 2008

16. Other co-morbidities of Age • Cancer • Cancer increasingly prevalent • Unclear if risk is truly increased • Renal Disease • Renal function slowly declines with age (espec > 70) • Certain HIV drugs can affect CrCl • Long-term effect on renal function unknown • Neurocognitive decline • As yet, no evidence of significant increased prevalence or earlier incidence • Frailty

17. Frailty in HIV • HIV associated with a >10-year earlier occurrence of a phenotype similar to frailty (MACS) • Risk increased with decreasing CD4 cell count, • Older age, lower educational level, and clinical AIDS were independently associated with frailty phenotype • Time with frailty phenotype independently associated with risk of AIDS or death, even after HIV suppression. Desquilbet L et al, J. Gerontol A Biol. Sci. Med. Sci. 62:1279-1286, 2007. Desquilbet L et al, J. Acquir. Immune Def. Syndr. 50:299-306, 2009. Onen N et al. J Infect. 59:346-52, 2009.

18. As patients get older, common diseases become more prevalent.Sorting the relevant impact of varying risk factors is difficultCommon tendency to ascribe an apparent increase to HIV or therapy is probably incorrect HIV Infection and or HAART Non-HIV related risk factors Co-morbidity Genetic Influences AGE

19. Management issues in older HIV+ve patient • Need for regular screening and health maintenance • Fasting lipids and glucose, renal function, bone disease • Cancer screening as would be performed in general population • www.europeanaidsclinicalsociety.org • Antiretroviral therapy • ?Earlier initiation • Choice of therapy to avoid metabolic and other toxicities • Management of Complications and co-morbidities • Prevention if possible • Manage other reversible factors -smoking • Polypharmacy - Awareness of drug-drug interactions • Recognition that HIV+ve patients may not respond as well • E.g. lipid-lowering therapy

20. Prevention and Management of Non-Infectious Co-Morbidities in HIV www.europeanaidsclinicalsociety.org